Nitric oxide (NO . ) has been widely studied as an active agent of many physiological and pathological processes. Currently, NO . divides attention with its sibling molecule, nitroxyl (HNO), mainly due to their differences in physiological responses broadening their applications. In order for NO . and HNO to have their multiple biological effects, they must reach quite specific concentrations in the body. This key issue makes it essential to develop strategies for delivering these molecules in a controlled and selective manner. The wide range of activities of these compounds along with smart strategies in the development of NO . /HNO donors have made them a hot spot. There are some NO . donor strategies in clinical use and also others in clinical trial, while HNO donors are further behind, illustrating the opportunities to come. Along these lines, we reviewed some current exciting NO . and HNO donor species, including organic‐ and inorganic‐based compounds, as well as nanomaterial platforms and NO . donor devices. This update may provide an overview of the systems currently available and how far we have come to meet multiple pharmacological needs.